Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.

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B Epitope Multiplicity and B/T Epitope Orientation Influence Immunogenicity of Foot-and-Mouth Disease Peptide Vaccines

Clinical and Developmental Immunology ◽

10.1155/2013/475960 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Esther Blanco ◽

Carolina Cubillos ◽

Noelia Moreno ◽

Juan Bárcena ◽

Beatriz G. de la Torre ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Neutralizing Antibodies ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitope ◽

T Cell Epitopes ◽

B Cell Epitope ◽

Foot And Mouth

Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFNγ. Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

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Inclusion of a specific T cell epitope increases the protection conferred against foot-and-mouth disease virus in pigs by a linear peptide containing an immunodominant B cell site

Virology Journal ◽

10.1186/1743-422x-9-66 ◽

2012 ◽

Vol 9 (1) ◽

pp. 66 ◽

Cited By ~ 13

Author(s):

Carolina Cubillos ◽

Beatriz G de la Torre ◽

Juan Bárcena ◽

David Andreu ◽

Francisco Sobrino ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitope ◽

Linear Peptide ◽

Mouth Disease Virus ◽

Foot And Mouth

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Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus

Vaccines ◽

10.3390/vaccines8030406 ◽

2020 ◽

Vol 8 (3) ◽

pp. 406

Author(s):

Sira Defaus ◽

Mar Forner ◽

Rodrigo Cañas-Arranz ◽

Patricia de León ◽

María J. Bustos ◽

...

Keyword(s):

T Cell ◽

Disease Virus ◽

Animal Health ◽

Unmet Need ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Mouth Disease Virus ◽

Foot And Mouth

A broadly protective and biosafe vaccine against foot-and-mouth disease virus (FMDV) remains an unmet need in the animal health sector. We have previously reported solid protection against serotype O FMDV afforded by dendrimeric peptide structures harboring virus-specific B- and T-cell epitopes, and also shown such type of multivalent presentations to be advantageous over simple B-T-epitope linear juxtaposition. Chemically, our vaccine platforms are modular constructions readily made from specified B- and T-cell epitope precursor peptides that are conjugated in solution. With the aim of developing an improved version of our formulations to be used for on-demand vaccine applications, we evaluate in this study a novel design for epitope presentation to the immune system based on a multiple antigen peptide (MAP) containing six immunologically relevant motifs arranged in dendrimeric fashion (named B2T-TB2). Interestingly, two B2T units fused tail-to-tail into a single homodimer platform elicited higher B- and T-cell specific responses than former candidates, with immunization scores remaining stable even after 4 months. Moreover, this macromolecular assembly shows consistent immune response in swine, the natural FMDV host, at reduced dose. Thus, our versatile, immunogenic prototype can find application in the development of peptide-based vaccine candidates for various therapeutic uses using safer and more efficacious vaccination regimens.

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